Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca-PIK3CA pathway.

Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both and . Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC.

Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.

NNFit: A Self-Supervised Deep Learning Method for Accelerated Quantification of High- Resolution Short Echo Time MR Spectroscopy Datasets.

Purpose To develop and evaluate the performance of NNFit, a self-supervised deep-learning method for quantification of high-resolution short echo-time (TE) echo-planar spectroscopic imaging (EPSI) datasets, with the goal of addressing the computational bottleneck of conventional spectral quantification methods in the clinical workflow. Materials and Methods This retrospective study included 89 short-TE whole-brain EPSI/GRAPPA scans from clinical trials for glioblastoma (Trial 1, May 2014-October 2018) and major-depressive-disorder (Trial 2, 2022- 2023). The training dataset included 685k spectra from 20 participants (60 scans) in Trial 1.

Impact of Frailty on Antihypertensive Treatment in Older Adults.

Background: The association between systolic blood pressure and all-cause mortality differs between frail and nonfrail individuals, highlighting uncertainties about the effectiveness of antihypertensive treatments in frail populations.

Methods: Using data from the SHEP trial (Systolic Hypertension in the Elderly Program), a baseline frailty index (FI), including 55 variables, was constructed. Fine-Gray subdistribution hazard models and Cox proportional hazards regression models were used to explore the association between baseline FI and the risks of stroke, cardiovascular disease, and all-cause death, as well as to examine whether the impact of antihypertensive treatment on these outcomes was modified by baseline FI.

Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History.

Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.

Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8.

Occurrence, Bioaccumulation, and Trophic Transfer of Short-Chain Chlorinated Paraffins (SCCPs) in a Marine Food Web from Laizhou Bay, Bohai Sea (Eastern China).

Short-chain chlorinated paraffins (SCCPs) are a persistent organic pollutant, and limited information is available on their bioaccumulation and trophic transfer, which would be affected by carbon chain length, chlorine content, and hydrophobicity. In this study, relevant data on SCCPs in water, sediments, and organisms collected from Laizhou Bay were analyzed to investigate the specific distribution of SCCPs and their bioaccumulation and trophic transfer. In water and sediments, the average SCCP concentrations (ΣSCCPs) were 362.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Fine-Needle Portosystemic Pressure Gradient as a Reference for Portal Hypertension in Patients with Intrahepatic Venovenous Shunt: A Prospective Study.

Purpose: To evaluate the consistency and agreement between portal venous pressure measured by fine-needle (F), portal vein catheterization (D), and hepatic vein balloon-occlusion (W) in decompensated cirrhotic patients with intrahepatic venovenous shunts (IHVS).

Materials And Methods: 156 consecutive patients planning to receive transjugular intrahepatic portosystemic shunt in our center were screened for study participation. The F/D/W were assessed for consistency by Pearson coefficient (r), linear regression coefficient (R), and intraclass correlation coefficient (ICC), and for disagreement (error exceeding 20% of D) by Bland-Altman method.

Association Between Time to Treatment and Outcomes of Endovascular Therapy vs Medical Management in Patients With Large Ischemic Stroke.

Background And Objectives: Randomized trials have proven the benefit of endovascular therapy (EVT) for acute large ischemic stroke. This study was to characterize the effect of time to treatment on benefit of EVT vs medical management (MM) among patients with large ischemic stroke.

Methods: This was a post hoc analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core randomized trial.

Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.

Weight loss with atogepant during the preventive treatment of migraine: A pooled analysis.

Background: Migraine is associated with obesity. These analyses evaluated weight change with atogepant used as a preventive migraine treatment.

Methods: Five atogepant clinical trials in adults with migraine (one phase 2b/3; four phase 3) were included: Three 12-week, randomized, placebo-controlled trials (episodic migraine: two; chronic migraine: one); one 40-week, open-label extension trial and one 52-week, standard care, randomized, long-term safety trial in episodic migraine.

Spatial resolution enhancement using deep learning improves chest disease diagnosis based on thick slice CT.

CT is crucial for diagnosing chest diseases, with image quality affected by spatial resolution. Thick-slice CT remains prevalent in practice due to cost considerations, yet its coarse spatial resolution may hinder accurate diagnoses. Our multicenter study develops a deep learning synthetic model with Convolutional-Transformer hybrid encoder-decoder architecture for generating thin-slice CT from thick-slice CT on a single center (1576 participants) and access the synthetic CT on three cross-regional centers (1228 participants).

Mechanical Properties, Durability Performance, and Microstructure of CaO-Fly Ash Solidified Sludge from Northeast, China.

In order to investigate the influence of the CaO and fly ash (FA) dosage and proportion on the mechanical properties, durability, and microstructure of solidified sludge, freeze-thaw (F-T) cycles and dry-wet (D-W) cycles are conducted to study the change in appearance and the strength attenuation of CaO-FA solidified sludge. Low-field nuclear magnetic resonance (LF-NMR) is used to analyze the microstructure of the solidified sludge with various dosages and ratios of CaO-FA. The results demonstrate that the unconfined compressive strength (UCS) and direct shear strength of solidified sludge increase with the prolongation of the curing age.

TYRP1 directed CAR T cells control tumor progression in preclinical melanoma models.

Despite therapeutic efficacy observed with immune checkpoint blockade in advanced melanoma, many tumors do not respond to treatment, representing a need for new therapies. Here, we have generated chimeric antigen receptor (CAR) T cells targeting TYRP1, a melanoma differentiation antigen expressed on the surface of melanomas, including rare acral and uveal melanomas. TYRP1-targeted CAR T cells demonstrate antigen-specific activation and cytotoxic activity and against human melanomas independent of the MHC alleles and expression.

Mesenchymal Stem Cell Exosome-Integrated Antibacterial Hydrogels for Nasal Mucosal Injury Treatment.

Hydrogels have emerged as appealing prospects for wound healing due to their superior biocompatible qualities. However, the integration of antibacterial active substances into hydrogels for effective wound repair remains challenging. Here, we present a novel double-network hydrogel for nasal mucosal injury repair with antibacterial and self-healing capabilities.

Opportunities to improve the diagnosis and treatment of primary hyperparathyroidism: retrospective cohort study.

Background: Although primary hyperparathyroidism (PHPT) is readily diagnosed biochemically and can be cured with low-risk surgery, it is often underrecognized and undertreated. Our objectives were to characterize, within our health system, how often patients with hypercalcemia were evaluated for PHPT and how often patients with PHPT underwent definitive treatment with parathyroidectomy.

Methods: Ambulatory patients aged 18 years or older seen at our health system between January 2018 and June 2023 with chronic hypercalcemia were identified from the medical record.

Deep Learning-based Unsupervised Domain Adaptation via a Unified Model for Prostate Lesion Detection Using Multisite Biparametric MRI Datasets.

Purpose To determine whether the unsupervised domain adaptation (UDA) method with generated images improves the performance of a supervised learning (SL) model for prostate cancer (PCa) detection using multisite biparametric (bp) MRI datasets. Materials and Methods This retrospective study included data from 5150 patients (14 191 samples) collected across nine different imaging centers. A novel UDA method using a unified generative model was developed for PCa detection using multisite bpMRI datasets.